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RESEARCH FOCUS AREAS:
- Non-small cell lung cancer
- Bone metastases
- Tumor microenvironment
- Resistance to targeted therapies
RESEARCH SUMMARY:
Lung cancer is the leading cause of cancer-related deaths in the United States, with the main driver being metastatic disease. The skeletal system is a frequent site of metastasis from lung cancer and other solid tumors, and causes major clinical challenges including pain, pathologic fractures, cord compression, and treatment resistance. My research focuses on developing patient-specific tumor-on-chip models incorporating human tumor microenvironments (TME) to evaluate novel drug therapies and predictive biomarkers in lung cancer, with an emphasis on studying the TME in bone metastases. We use patient-derived cancer organoids (PDCOs), human primary stromal cells, and cancer cell lines in 3D microfluidic devices to investigate how bone stromal cells affect functional and molecular responses to targeted drug therapies. To interrogate whether findings in our chip can translate to clinical use, we employ a semi-automated circulating tumor cell (CTC) enrichment platform to assess global molecular changes, identify tumor heterogeneity, and advance biomarker discovery in lung cancer. Our overall goal is to identify stromal-mediated mechanisms of resistance and develop new strategies to address treatment-refractory lung cancer.
EDUCATION:
- BS in Biological Sciences, University of Illinois Chicago
- MD PhD in Cancer Biology, University of Chicago, Pritzker School of Medicine
- Residency in Internal Medicine, University of Wisconsin Hospitals and Clinics
- Fellowship in Medical Oncology, University of Wisconsin Hospitals and Clinics
SELECT PUBLICATIONS:
- A clinical-grade liquid biomarker detects neuroendocrine differentiation in prostate cancer Zhao, SG; Sperger, JM; Schehr, JL; McKay, RR; Emamekhoo, H; Singh, A; Schultz, ZD; Bade, RM; Stahlfeld, CN; Gilsdorf, CS; Hernandez, CI; Wolfe, SK; Mayberry, RD; Krause, HM; Bootsma, M; Helzer, KT; Rydzewski, N; Bakhtiar, H; Shi, Y; Blitzer, G; Kyriakopoulos, CE; Kosoff, D; Wei, XX; Floberg, J; Sethakorn, N; Sharifi, M; Harari, PM; Huang, W; Beltran, H; Choueiri, TK; Scher, HI; Rathkopf, DE; Halabi, S; Armstrong, AJ; Beebe, DJ; Yu, M; Sundling, KE; Taplin, ME; Lang, JM Journal of Clinical Investigation 2022 Nov 1;132(21):e161858. doi: 10.1172/JCI161858. PMID: 36317634; PMCID: PMC9621140
- Longitudinal molecular profiling of circulating tumor cells in metastatic renal cell carcinoma Bootsma, M; McKay, RR; Emamekhoo, H; Bade, RM; Schehr, JL; Mannino, MC; Singh, A; Wolfe, SK; Schultz, ZD; Sperger, J; Xie, W; Signoretti, S; Kyriakopoulos, CE; Kosoff, D; Abel, EJ; Helzer, KT; Rydzewski, N; Bakhtiar, H; Shi, Y; Blitzer, G; Bassetti, M; Floberg, J; Yu, M; Sethakorn, N; Sharifi, M; Harari, PM; Choueiri, TK; Lang, JM; Zhao, SG Journal of Clinical Oncology 2022 Nov 1;40(31):3633-3641. doi: 10.1200/JCO.22.00219. Epub 2022 May 26. PMID: 35617646; PMCID: PMC9622626
- Integrated analysis of the tumor microenvironment using a reconfigurable microfluidic cell culture platform Sethakorn, N; Heninger, E; Breneman, MT; Recchia, E; Ding, AB; Jarrard, DF; Hematti, P; Beebe, DJ; Kosoff, D FASEB Journal 2022 Oct;36(10):e22540. doi: 10.1096/fj.202200684RR. PMID: 36083096; PMCID: PMC9476232
- Analytical validation and initial clinical testing of quantitative microscopic evaluation for PD-L1 and HLA I expression on circulating tumor cells from patients with non-small cell lung cancer Schehr, JL; Sethakorn, N; Schultz, ZD; Hernandez, CI; Bade, RM; Eyzaguirre, D; Singh, A; Niles, DJ; Henderson, L; Warrick, JW; Berry, SM; Sundling, KE; Beebe, DJ; Leal, TA; Lang, JM Biomarker Research 2022 Apr 25;10(1):26. doi: 10.1186/s40364-022-00370-8. PMID: 35468853; PMCID: PMC9040226
- Advancing treatment of bone metastases through novel translational approaches targeting the bone microenvironment Sethakorn, N; Heninger, E; Sánchez-de-Diego, C; Ding, AB; Yada, RC; Kerr, SC; Kosoff, D; Beebe, DJ; Lang, JM Cancers (Basel) 2022 Feb 1;14(3):757. doi: 10.3390/cancers14030757. PMID: 35159026; PMCID: PMC8833657
- Live cell molecular analysis of primary prostate cancer organoids identifies persistent androgen receptor signaling Heninger, E; Kosoff, D; Rodems, TS; Sethakorn, N; Singh, A; Gungurthi, H; Carlson, KN; Yang, B; Gilsdorf, C; Pasch, CA; Deming, DA; Ellis, L; Beebe, DJ; Jarrard, DF; Lang, JM. Medical Oncology 2021 Sep 28;38(11):135. doi: 10.1007/s12032-021-01582-y. PMID: 34581895; PMCID: PMC8478748
- Immune profiling of the bone marrow microenvironment in patients with high-risk localized prostate cancer Heninger, E; Sethakorn, N; Kosoff, D; Hematti, P; Kuczler, MD; Pienta, KJ; Lang, JM Oncotarget 2020 Nov 17;11(46):4253-4265. doi: 10.18632/oncotarget.27817. PMID: 33245727; PMCID: PMC7679037
- Identification of PD1-mediated regulation of antitumor antigen response in patients with NSCLC using the trans vivo DTH assay Lema, DA; Jankowska-Gan, E; Sethakorn, N; Burlingham, W; Leal, T Journal for Immunotherapy of Cancer 2020 Jun;8(1):e000152. doi: 10.1136/jitc-2019-000152. PMID: 32527929; PMCID: PMC7292037
- Spectrum of genomic alterations in FGFR3: current appraisal of the potential role of FGFR3 in advanced urothelial carcinoma Sethakorn, N; O'Donnell, PH BJU International 2016 Nov;118(5):681-691. doi: 10.1111/bju.13552. Epub 2016 Jul 7. PMID: 27271022
- T-oligo as an anticancer agent in colorectal cancer Wojdyla, L; Stone, AL; Sethakorn, N; Uppada, SB; Devito, JT; Bissonnette, M; Puri, N Biochemical and Biophysical Research Communications 2014 Apr 4;446(2):596-601. doi: 10.1016/j.bbrc.2014.03.013. Epub 2014 Mar 12. PMID: 24632202; PMCID: PMC4843172
FULL LIST OF PUBLICATIONS
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